This proposal is concerned with the evaluation of the therapeutic value of fructose-1,6-diphosphate (FDP) when administered intravenously during the oligemic phase of the shock (30-35 mm Hg mean arterial pressure for three hours) which has been shown to be irreversible to the infusion of all shed blood. Experiments completed by the investigator indicate that increase in the rate of an aerobic glycolysis in the myocardium and other organs during the early phase is a function of the severity of the hypotension. However, when acidosis takes place, glycolysis progressively ceases due to the inactivation of the pH sensitive enzyme phosphofructokinase (PFK). Analysis of the data obtained in these studies and others indicate that FDP is a metabolic regulator capable of influencing PFK and pyruvate kinase activity in both ischemic and normally oxygenated myocardium and other organs and tissues. When administered intravenously to animals at the beginning of the hypotension or 30 min after the onset of shock, all of them survived while the controls (not treated) died within 24 hours. FDP also prevents myocardial depletion of ATP and creatine phosphate in the non-treated animals sacrificed prior to retransfusion. As hemorrhagic and endotoxic shock share in common an endogenous energy production deficit, we assessed the therapeutic effect of FDP in dogs subjected to lethal doses of endotoxin. FDP in the endotoxic model prevented circulatory collapse, conserved renal function, prevented intestinal bleeding and fluid loss, protected intestinal mucosa from hemorrhagic necrosis, and 90% survival was achieved. The experiments of this proposal are designed to determine at what point in time during the oligemic phase of the shock FDP administration will still prevent fatal outcome. The data obtained will perhaps substantiate the hypothesis that irreversibility in this condition is due to acute cardiac failure and that this is related to impaired myocardial metabolism. The animal model in this study will be dogs. The preliminary data indicates that this intervention should be of clinical importance in conditions where an endogenous energy production deficit arising from impaired oxidative metabolism cannot be compensated for by glycolysis.